Various diseases and disorders are associated with inflammation. Inflammation is a process associated with recruitment of inflammatory cells (e.g., leukocytes) to a site of injury or infection. Inflammation generally protects the body from infection and injury. However, excessive or inappropriate inflammation can have deleterious effects. Autoimmune disorders, for example, often trigger inflammation resulting in the destruction of normal body tissues. Inflammation is also linked to cancer. See, e.g., Coussens et al. (2002) Nature 420:860-867. For example, chronic inflammation associated with inflammatory bowel disease (IBD) is strongly correlated with colon carcinogenesis. During the inflammatory response, certain inflammatory cells produce agents that promote angiogenesis, reduce the anti-tumor activity of cytotoxic T-cells, and induce mutations in DNA, thus creating an environment the promotes tumor progression. Id.
IL-23 is a heterodimeric cytokine that plays a dominant role in autoimmune/inflammatory disorders, and in particular, chronic inflammation. For example, studies in mice have revealed that IL-23 is essential for development of experimental allergic encephalomyelitis (autoimmune inflammation of the brain), which is a model for multiple sclerosis; collagen-induced arthritis, which is a model for rheumatoid arthritis; and delayed-type hypersensitivity. IL-23 also functions to maintain established colitis (a form of IBD). Transgenic expression of IL-23 leads to systemic inflammatory response, and dysregulation of IL-23 leads to eczematous skin disease (an inflammatory skin condition). IL-23 stimulates a unique population of T cells (ThIL-17 cells), which in turn induce the production of IL-17 and proinflammatory cytokines. For review of the roles of IL-23 in inflammation and autoimmunity, see, e.g., Hunter (2005) Nat. Rev. Immunol. 5:521-531; and Holscher (2005) Curr. Opin. Invest. Drugs 6:489-495. IL-23 has also been shown to promote tumor growth by increasing angiogenesis and decreasing tumor infiltration by cytotoxic T cells. Langowski et al. (2006) Nature 442:461-465.